But the Barca captain was named in Ernesto Valverde's starting XI on Saturday and scored both goals as the league leaders took another step towards the title.
The 31-year-old opened the scoring with a free-kick in the 71st minute before slotting into the bottom corner after Malcom cut back to him.
Messi is now on 31 goals for the season in La Liga, while he recorded his 334th victory in the Spanish top-flight, matching former Real Madrid goalkeeper Iker Casillas.
A tough week might have impacted other forwards, but Busquets always expects the unexpected from Messi.
"He is so important for us and he had a great game," Busquets said. "It is always an advantage to have him playing for us.
"His performances may be unusual from the outside, but they do not surprise us. What he does in training is more difficult in matches, but we are used to it."
Describing Barca's difficulties in breaking down Espanyol, who held out until the 71st minute, Busquets said: "Espanyol took an ultra-defensive approach where it was difficult to find spaces.
"But we still had chances and they did not. In the end, despite the fact that it was difficult, we have got the goals and won - deservedly after what you could see on the field."
Barca are now 13 points ahead of second-placed Atletico Madrid in La Liga and are back in action on Tuesday before taking on their nearest challengers at Camp Nou.